Case Report
Groningen Syphilis. The great imitator strikes again


    Anne JM Slot1, Hendrik W Zijlstra1, Tanly Su2, Maartje A van den Boomgaard3, J Marja Oldhoff2, Charlotte HSB van den Berg1

    Departments of 1Critical Care, 2Dermatology and 3Infectious diseases University Medical Center Groningen,  Groningen, the Netherlands


    A.J.M. Slot -
    Case Report

    Groningen Syphilis. The great imitator strikes again


    Syphilis is a sexually transmitted infection caused by Treponema pallidum spp pallidum, with a very low incidence in women in the Netherlands.  Syphilis can present in several stages and because of the various clinical manifestations it is referred to as “the great imitator”.

    We  describe the case of a 42-year-old woman presenting with hoarseness and difficulty breathing due to a supraglottic mass, primarly suspected for oropharyngeal carcinoma. Because of the variety of symptoms and her sexual history a sexually transmitted infection was suspected. After the diagnosis was confirmed she was treated succesfully.


    Syphilis is a sexually transmitted infection that can be divided in to three stages that can overlap at the time of presentation (1,2). The presentation is often atypical and syphilis is therefore frequently referred to as “the great imitator”. In2020, an average of 10.8% of tested sex workers worldwide had an active syphilis infection (3). The incidence in the Netherlands in women is very low: women accounted for only 0.1% of new syphilis diagnoses in the Netherlands in 2021 (n=1378). We would like to present a case of syphilis with an airway obstruction.

    Case report:

    A 42-year-old woman with a medical history of post-traumatic stress disorder and drug abuse presented in the emergency department with hoarseness and difficulty breathing. Besides an C-reactive protein of 124 mg/L, laboratory tests were unremarkable. A CT scan showed a supraglottic mass, bilateral swelling of cervical lymph nodes and osteolytic lesions of the cervical spine. An endoscopy revealed a mass of the tongue base with white coating (figure 1) and nearly complete supraglottic airway obstruction due to swelling of the aryepiglottic folds. Additionally, there were painful skin lesions, otorrhea, swollen eyes and flu-like symptoms.  After an awake nasotracheal intubation several biopsies were taken. Additional examination in the ICU showed a sharply demarcated ulcer with an indurated base on the labium majus. Furthermore multiple lenticular red papules and nodules, some with central erosion disseminated over face, trunk and extremities. The ear canal showed yellow discharge and her right elbow was painful, red, and swollen. Hetero anamnesis revealed that the patient recently stopped her activities as an illegal sex worker. With this information further tests were initiated. T. pallidum Particle Agglutination (TPPA), confirmation blot and Rapid Plasma Reagin (RPR) were positive( 1:32). HIV antigen/antibody test was negative, as were Chlamydia trachomatis, Neisseria Gonorrhoeae PCR and a pregnancy test. Because of the severity of illness and suspicion of otitis luetica the patient was treated with 18 million IU benzathine benzylpenicillin per 24 hours intravenously daily, pending diagnostic tests.

    Figure 1 - Endoscopic view of supraglottic swelling

    The skin biopsy showed a superficial spongiotic dermatitis rich in plasma cells and granulomas, without evidence of spirochetes. The tongue base biopsy  was partially necrotic, with chronic inflammation and no malignancy. The lymph node biopsy showed granulomatous inflammation and immunohistochemical stain for T. pallidum revealed spirochetes (figure 2). Both cerebrospinal fluid (CSF) (RPR <2 and TPPA index liquor/serum of 0.74, consistent with no intrathecal antibody synthesis)  and ocular analysis showed no signs of neurosyphilis.

    Figure 2 – Lymph node biopsy with Treponema pallidum, spp pallidum (red/brown) detectable.

    After initiation of therapy the skin lesions,arthritis and tongue base swelling resolved rapidly. The spouse was advised to get tested.

    Outpatient follow up showed complete recovery after seven with negative RPR (1:<2).


    Syphilis (also known as lues) is caused by Treponema pallidum spp pallidum a motile Gram-negative spirochete. The overall incidence of syphilis in the female population in The Netherlands is very low. Only 21 of the 1378 patients with syphilis presenting in Sexual Health Centres in the Netherlands were female.(4) Presumably the incidence in illegal sex workers is higher.

    The clinical manifestation depends on the stage.(2) Primary syphilis (stage 1)  occurs in the first weeks after infection and presents as a typically  painless ulcer, usually on the genitalia, also called chancre. Secondary syphilis (stage 2) is a systemic illness, with a wide variety of clinical manifestations, including adenopathy, rash, synovitis, otitis and gastrointestinal disease. Tertiary syphilis (stage 3) is characterized as cardiovascular syphilis, with dilatation of the thoracic aorta and aortic valve regurgitation, neurosyphilis or as gummatous disease. Gummatous syphilis is rare and consists of granulomatous disease of skin, bones and viscera. Stage 3 can develop years after primary infection in approximately a third of untreated patients(5).

    The diagnostic approach consist of serum TPPA, indicating antibodies against Treponema and therefore previous exposure. RPR is the activity against the infection and consistent with an active infection and is  used for treatment response. Neurosyphilis can occur without symptoms. In our patient were ocular symptoms and otorrhea, therefore a CSF was drawn and the CSF/serum index calculated. (9)

    The mainstay of syphilis treatment is penicillin, the dose depends on the stage and clinical symptoms. (6, 7)

    Stage 1 and 2 can overlap at the time of presentation, but concomitant stage 2 and 3 has not been described in recent literature. Our patient had clinical manifestations of syphilis in various stages: the chancre of stage 1, multiple symptoms of stage 2 such as  otosyphilis and arthritis. Osteolytic lesions have rarely been described in stage 2(8).  There was a possibility of gummatous disease of stage 3. However because the biopsy of the tumour showed no granulomas, there is no clear evidence. Because the rarity of this manifestation, no definite proof of gumma and multiple signs of stage 1 and 2 syphilis, gummatous disease was deemed unlikely.

    Taking a thorough medical history and physical examination remains vitally important in ICU patients. The combination of symptoms and her history of being a sex worker made this a likely diagnosis. Occam’s razor states that “entities must not be multiplied beyond necessity", thus if a diagnosis can explain all symptoms, it is more likely than multiple different etiologies. In this case all symptoms could be explained by syphilis.


    Since syphilis numbers are rising we would like to point out that this ancient but relatively easy treatable diagnosis should be in your differential diagnosis with poorly understood masses/swelling and when other symptoms are not understood, especially in sex workers and men who have sex with men.


    Disclosures: All authors declare no conflict of interest. No funding or financial support was received.

    Author agreement: All authors certify that they have seen and approved the manuscript being


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